Giant Blue Nevus: A New Association to Nevus of Ota.

Nevus of Ota, also known as oculodermal melanocytosis, is a congenital pigmentary condition that can affect structures in the distribution of the ophthalmic and maxillary divisions of the trigeminal cranial nerve. Malignant transformation, although rare, may occur within nevus of Ota and result in uveal, cutaneous, orbital or even dural melanoma. We present a new association of Nevus of Ota complicated with a giant orbital Blue Nevus in a young white male and the management of this tumor.

BRAF V600E and KRAS G12S mutations in peripheral nerve sheath tumours.

AIMS: Benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumours occur either sporadically or are related to neurofibromatosis (NF). The mechanisms involved are well known in NF-related tumours, but still remain unclear in sporadic cases. Somatic BRAF and KRAS mutations represent the most frequent genetic events in melanocytic neoplastic lesions. Because melanocytes and Schwann cells both derive from neural crest cells, we hypothesized that BRAF and KRAS mutations might influence BPNST and MPNST development. METHODS AND RESULTS: BRAF exon 15 and KRAS exons 2 and 3 polymerase chain reaction (PCR) sequencing was performed in formalin-fixed/paraffin-embedded samples of 99 BPNST and MPNST, related and non-related to NF types 1 and 2. Oncogenic BRAF V600E mutations were found in four of 40 schwannomas (including one acoustic neuroma) and one of 13 MPNST, not associated with NF. A KRAS G12S mutation was also evident in one sporadic schwannoma. CONCLUSION: Our findings suggest that RAS pathway activation due to BRAF V600E and KRAS mutations is an important event in a subset of peripheral nerve sheath tumours not related to NF.

Preventive midline laparotomy closure with a new bioabsorbable mesh: an experimental study.

BACKGROUND: Incisional hernia formation is one of the most frequent complications of midline laparotomies requiring reoperation. The aim of this study was to evaluate the safety and efficacy of prophylactically placing a biodegradable mesh within the incision site at closure in a rat model. METHODS: A 4-cm full-thick midline laparotomy was made in Sprague-Dawley rats along the linea alba and closed by inserting a commercially available web of synthetic polymers (polyglycolic acid-trimethylene carbonate) that are slowly degraded by the body. Host tissue reaction was evaluated ex vivo and compared with that obtained in suture-only-treated rats. Specimens were harvested at 1, 3, and 6mo after surgery and divided for histologic and zymographic analyses and uniaxial material testing. A group of intact nonoperated animals were included to serve as a reference. RESULTS: The excised tissue explants revealed that the performance of the synthetic device was good and resulted in enhanced fibroproliferation, gelatinolytic activity, and angiogenesis within the repair site as compared with the suture-only procedure. Lastly, tensile strength augmented over the suture-only condition. CONCLUSIONS: The preventive introduction of an absorbable mesh stimulates new tissue ingrowth and performance relative to suture repair without prosthesis, probably contributing to eventually reinforce the tension line. These results have a clinical potential in abdominal wall closure, especially in patients with multiple risk factors such as those treated for aortic reconstructive surgery, without the short- and long-term complications related to permanent grafts. However, data are preliminary and should be confirmed with longer follow-ups.

Apoptosis-like cell death induction and aberrant fibroblast properties in human incisional hernia fascia.

Incisional hernia often occurs following laparotomy and can be a source of serious problems. Although there is evidence that a biological cause may underlie its development, the mechanistic link between the local tissue microenvironment and tissue rupture is lacking. In this study, we used matched tissue-based and in vitro primary cell culture systems to examine the possible involvement of fascia fibroblasts in incisional hernia pathogenesis. Fascia biopsies were collected at surgery from incisional hernia patients and non-incisional hernia controls. Tissue samples were analyzed by histology and immunoblotting methods. Fascia primary fibroblast cultures were assessed at morphological, ultrastructural, and functional levels. We document tissue and fibroblast loss coupled to caspase-3 activation and induction of apoptosis-like cell-death mechanisms in incisional hernia fascia. Alterations in cytoskeleton organization and solubility were also observed. Incisional hernia fibroblasts showed a consistent phenotype throughout early passages in vitro, which was characterized by significantly enhanced cell proliferation and migration, reduced adhesion, and altered cytoskeleton properties, as compared to non-incisional hernia fibroblasts. Moreover, incisional hernia fibroblasts displayed morphological and ultrastructural alterations compatible with autophagic processes or lysosomal dysfunction, together with enhanced sensitivity to proapoptotic challenges. Overall, these data suggest an ongoing complex interplay of cell death induction, aberrant fibroblast function, and tissue loss in incisional hernia fascia, which may significantly contribute to altered matrix maintenance and tissue rupture in vivo.

Soft tissue solitary fibrous tumor. Imaging findings in a series of nine cases.

OBJECTIVE: Few articles have been published regarding the imaging characteristics of soft tissue solitary fibrous tumors (SFT). The aim of this study is to describe the radiological features in a series of nine patients and to compare these results with pathological and clinical outcome. SUBJECTS AND METHODS: Nine cases of soft tissue SFT, confirmed by an experienced tumor pathologist, were studied with imaging techniques (US and MRI). Tumor location, size, morphology, local invasion, vascularity, MRI signal intensities, and dynamic contrast-enhancement patterns were recorded. Tumors were subclassified into cellular, fibrous, and giant cell forms histologically. RESULTS: The most common findings were a well-defined, polylobulated mass that tended to displace adjacent structures. The extremities were the most frequent site of presentation. The tumors showed high vascularity in all imaging studies. The radiological features that correlated better with malignant criteria were tumor size, heterogeneous signal intensity, and heterogeneous uptake of contrast on MRI. On dynamic contrast-enhanced (DCE) sequences, three tumors showed a biphasic curve (type IV) and one a progressive uptake curve (type II). The latter recurred twice after extensive local surgery and was classified as a giant cell variant. CONCLUSION: In this study a retrospective review of nine new cases of soft tissue SFT was carried out. The presence of a large solid, highly vascularized mass with a prominent vascular pedicle that displaces adjacent structures may suggest the diagnosis of an SFT. DCE sequences might help identify those tumors with worse clinical outcome, but a study with a larger series of patients is needed.

Full face transplant: the first case report.

BACKGROUND: Since 2005, 11 human face transplants have been performed. In each, varying amounts of tissue have been transplanted. Herein we report a "full" face transplant including all intact aesthetic and functional units. METHODS: On March 27, 2010, we performed a full face transplant, including all the soft tissues and part of the underlaying bony structure, at the University Hospital Vall d'Hebron, Barcelona, Spain. The donor was a 41-year-old male, who died from a massive brain hemorrhage. The recipient was a 30-year-old male with a severe facial deformity caused by a ballistic trauma in 2005. Harvest and subsequent implant took 24 hours. The patient received initial induction (Thymoglobulin 2 mg/kg/iv; Prednisone 1 gm/iv) and maintenance (Prednisone 1 mg/kg/24hours, Tacrolimus 10-15 ng/mL/PO, and Mycophenolate mofetil 2g/daily/PO) immunosuppression and Infection prophylaxis (Valganciclovir and Co-trimoxazole). RESULTS: There were no intraoperative complications. Postoperative complications included; venous anastomoses thrombosis, acute oro-cutaneous fistula, right parotid sialocele and 2 acute rejection episodes, which were resolved by revision of the anastomosis, profuse irrigation and immunotherapy adjustment, respectively. The patient was discharged from the hospital at 4 months posttransplant with; near-total sensation and partial-motor recovery, no psychological complications and excellent acceptance of his new facial appearance. CONCLUSIONS: The early success described in this case report demonstrates the technical and clinical feasibility of transplanting all the tissues of the with all its aesthetic and functional units intact.

Multicentric liposarcoma.

Liposarcoma is one of the most common malignant soft tissue tumours. It usually presents as a single mass, and the prognosis varies according to the degree of histological differentiation. Multicentric liposarcoma is an unusual presentation of this tumour in which several independent lesions develop and generally display an aggressive pattern. It may be difficult to establish a precise diagnosis because of the problems differentiating between recurrence or metastasis of a single liposarcoma and multicentric primary lesions. A systematic review was undertaken, assessing articles on multicentric liposarcoma, with emphasis on the diagnostic criteria and treatment for this condition. Illustrative cases of multicentric liposarcoma from our Institution are presented.

Thyroid orbitopathy obscuring the diagnosis of a rare neuromuscular hamartoma of the superior rectus muscle in an adult.

A neuromuscular hamartoma is a rare benign tumour that is most frequently associated with peripheral nerves. The authors present a case of a 61 year-old man with bilateral exophthalmos and lid retraction who developed further proptosis and chemosis in the left eye over a five month period. An initial diagnosis of thyroid orbitopathy was made and he had a limited response to two courses of oral steroid administered in another centre. He was subsequently referred to our institution for further management when his condition worsened following withdrawal of treatment. Orbital CT scan showed a thickening of the recti muscles and particularly the left superior rectus and overlying soft tissue. Given this unusual pattern of muscle involvement in thyroid orbitopathy, a muscle biopsy was performed. This showed the presence of a neuromuscular hamartoma without malignant features. The orbital fat biopsy showed no pathological findings. A neuromuscular hamartoma not associated with a peripheral nerve is a rare entity, especially when coupled with an extraocular muscle. We wish to highlight the importance of a muscle biopsy when faced with a clinical picture and radiological pattern of extraocular muscle enlargement not typical of what we know to occur traditionally in thyroid eye disease.

MMPs/TIMPs and inflammatory signalling de-regulation in human incisional hernia tissues.

BACKGROUND: Incisional hernia is a common and important complication of laparotomies. Epidemiological studies allude to an underlying biological cause, at least in a subset of population. Interest has mainly focused on abnormal collagen metabolism. However, the role played by other determinants of extracellular matrix (ECM) composition is unknown. To date, there are few laboratory studies investigating the importance of biological factors contributing to incisional hernia development. We performed a descriptive tissue-based analysis to elucidate the possible relevance of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in association with local cytokine induction in human incisional hernia tissues. The expression profiles of MMPs, TIMPs and pro-inflammatory cytokine signalling were investigated in aponeurosis and skeletal muscle specimens taken intraoperatively from incisional hernia (n= 10) and control (n= 10) patients. Semiquantitative RT-PCR, zymography and immunoblotting analyses were done. Incisional hernia samples displayed alterations in the microstructure and loss of ECM, as assessed by histological analyses. Moreover, incisional hernia tissues showed increased MMP/TIMP ratios and de-regulated inflammatory signalling (tumor necrosis factor [TNFA] and interleukin [IL]-6 tended to increase, whereas aponeurosis TNFA receptors decreased). The changes were tissue-specific and were detectable at the mRNA and/or protein level. Statistical analyses showed several associations between individual MMPs, TIMPs, interstitial collagens and inflammatory markers. The increment of MMPs in the absence of a counterbalance by TIMPs, together with an ongoing de-regulated inflammatory signalling, may contribute in inducing a functional defect of the ECM network by post-translational mechanisms, which may trigger abdominal wall tissue loss and eventual rupture. The notable TIMP3 protein down-regulation in incisional hernia fascia may be of pathophysiological significance. We conclude that this study may help to pinpoint novel hypotheses of pathogenesis that can lead to a better understanding of the disease and ultimately to improvement in current therapeutic approaches.

Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis.

Pseudoarthrosis is a relatively frequent complication of fractures, in which the lack of mechanical stability and biological stimuli results in the failure of bone union, most frequently in humerus and tibia. Treatment of recalcitrant pseudoarthrosis relies on the achievement of satisfactory mechanical stability combined with adequate local biology. Herein we present two cases of atrophic pseudoarthrosis that received a tissue-engineering product (TEP) composed of autologous bone marrow-derived mesenchymal stromal cells (BM-MSC) combined with deantigenized trabecular bone particles from a tissue bank. The feasibility of the treatment and osteogenic potential of the cell-based medicine was first demonstrated in an ovine model of critical size segmental tibial defect. Clinical-grade autologous BM-MSC were produced following a good manufacturing practice-compliant bioprocess. Results were successful in one case, with pseudoarthrosis resolution, and inconclusive in the other one. The first patient presented atrophic pseudoarthrosis of the humeral diaphysis and was treated with osteosynthesis and TEP resulting in satisfactory consolidation at month 6. The second case presented a recalcitrant pseudoarthrosis of the proximal tibia and the Masquelet technique was followed before filling the defect with the TEP. This patient presented a neuropathic pain syndrome unrelated to the treatment that forced the amputation of the extremity 3 months later. In this case, the histological analysis of the tissue formed at the defect site provided evidence of neovascularization but no overt bone remodelling activity. It is concluded that the use of expanded autologous BM-MSC to treat pseudoarthrosis was demonstrated to be feasible and safe, provided that no clinical complications were reported, and early signs of effectiveness were observed. Copyright © 2016 John Wiley & Sons, Ltd.

Benign lymphangiomatous papules of the skin associated with ovarian fibroma.

Benign lymphangiomatous papules of the skin are considered reactive lymphatic proliferations either caused by disruption of the lymphatic flow or tissue damage produced by operation or radiation therapy. We report a 72-year-old woman with umbilical papules and vesicle-like lesions that led to the diagnosis of a large ovarian fibroma. Histologic study revealed dilated lymphatic spaces manifesting an anastomosing and branched pattern in the papillary and reticular dermis dissecting collagen bundles. The vessels were lined by plump endothelial cells with foci of intravascular papillary endothelial cell hyperplasia. After the ovarian fibroma was removed by laparotomy, umbilical lesions almost disappeared, leaving small flesh-colored papules. A periumbilical dermatosis may herald certain intra-abdominal diseases including those of neoplastic derivation. A heightened awareness of this association may lead to an early diagnosis with a potential for improved patient outcome. Benign lymphangiomatous papules have not been previously described in association with an untreated tumor, without previous operation or radiotherapy. This case advocates for disruption of the lymphatic drainage as the probable pathogenetic mechanism.

[Endolymphatic sac tumour as an infrequent cause of Ménière's syndrome]. / Tumor de saco endolinfático como causa infrecuente de síndrome de Ménière.

Endolymphatic sac tumours are uncommon. They have been classified as adenocarcinomas with a low degree of malignancy and no metastases have yet been documented. We report on a female patient with Von Hippel-Lindau disease and Ménière's syndrome suffering from an endolymphatic sac tumour. Diagnosis and early treatment are essential to preserve hearing, so long-term monitoring is recommended when this clinical combination is encountered.

Primary monophasic synovial sarcoma of the duodenum confirmed by cytogenetic analysis with demonstration of t(X;18): a case report.

Synovial sarcoma (SS) is an uncommon malignant neoplasm of the soft tissues. It mainly affects the periarticular tissues of the extremities in young adults, but has been described at nearly all sites; nevertheless, the gastrointestinal tract is an exceptional location. We report a case of a primary synovial sarcoma of the duodenum in a 69-year-old woman. Histological study showed a monophasic pattern. The tumor cells demonstrated diffuse vimentin and Bcl-2 expression, partial EMA expression and focal AE1/3 positivity. The differential diagnosis includes gastrointestinal stromal tumors. Cytogenetic analysis confirmed the diagnosis, with detection of the X;18 translocation. The patient presented postoperative complications and died one month following the intervention.

Successful treatment of pulmonary metastatic salivary ductal carcinoma with trastuzumab-based therapy.

BACKGROUND: Salivary ductal carcinoma (SDC) is an uncommon malignant tumor of the salivary glands. Although there is no known standard of care for the treatment of advanced disease, the vast majority of patients with SDC may be offered palliative systemic therapy. We report a case of epidermal growth factor receptor 2 (HER2)-positive metastatic submandibular SDC with a complete and durable clinical response to treatment with trastuzumab in combination with chemotherapy. METHODS AND RESULTS: A 62-year-old man was diagnosed with SDC of the left submandibular gland with extensive cervical lymph node involvement. The lesion was completely resected, and the patient underwent postoperative radiotherapy. After 6 months, multiple pulmonary metastatic lesions were detected. A complete response was reached with trastuzumab-based combination therapy, and no evidence of disease progression has been observed after 14 months of initiation of systemic therapy. CONCLUSION: Trastuzumab-based combination therapies should be considered for advanced SDC.

Lower somatostatin expression is an early event in diabetic retinopathy and is associated with retinal neurodegeneration.

OBJECTIVE: To test the hypothesis that a reduction of somatostatin (SST) in the retina exists in patients without clinically detectable diabetic retinopathy and that it is associated with retinal neurodegeneration. RESEARCH DESIGN AND METHODS: Human diabetic postmortem eyes (n = 10) without clinically detectable retinopathy were compared with eyes (n = 10) from nondiabetic donors. SST mRNA (RT-PCR) and SST-28 immunoreactivity (confocal laser) were measured separately in neuroretina and retinal pigment epithelium (RPE). In addition, SST-28 (radioimmunoassay) was measured in the vitreous fluid. Glial fibrillar acidic protein (GFAP) was assessed by immunofluorescence and Western blot. Apoptotic cells were quantified using transferase-mediated dUTP nick-end labeling. RESULTS: A higher expression of SST was detected in RPE than neuroretina in both groups. SST mRNA levels and SST-28 immunoreactivity were significantly lower in both RPE and the neuroretina from diabetic donors compared with nondiabetic donors. These results were in agreement with those obtained by measuring SST-28 in the vitreous fluid of the same donors. Increased GFAP and a higher degree of apoptosis were observed in diabetic retinas compared with nondiabetic retinas. These changes were most evident in patients with the higher deficit of SST. CONCLUSIONS: Underproduction of SST is an early event in the eyes of diabetic patients and is associated with glial activation and neural death. In addition, our results suggest that RPE is an important source of SST in the human eye. The possible role of the lower production of SST in the pathogenesis of diabetic retinopathy requires further investigation.

Intraosseous haemangioma of the ilium.

Intraosseous haemangioma, an uncommon benign vascular tumour, is most commonly seen in adults and tends to involve the vertebrae and the skull. Lesions of flat bones are rare and the imaging findings in these patients are non-specific. We report a unique case of intraosseous haemangioma in the ilium of a 7-year-old girl studied by US, radiography, scintigraphy, CT and MRI.

Intraosseous intraneural perineurioma: report of a case with morphological, immunohistochemical and FISH study.

We report a case of an intramandibular intraneural perineurioma developed in the left dentary nerve. This tumour is rare and shows a typical histological, immunohistochemical and ultrastructural appearance: concentric whorls of perineurial cells EMA+ and PS100- around nerve fibers. This tumour must be distinguished from extraneural or soft tissue perineurioma, also composed of perineurial cells, with distinct clinical presentation and histological appearance, and from localized hypertrophic neuropathy, a reactive process frequently identified with intraneural perineurioma. Cytogenetic evidence for the neoplastic nature of this tumour is also presented in this report.

Serum concentrations of laminin-P1 in thrombotic microangiopathy: usefulness as an index of activity and prognostic value.

Laminin is the main noncollagenous constituent of the basement membrane, and its serum levels could reflect the metabolic changes that occur in the basement membrane. Severe endothelial injury with thickening of basement membrane is a characteristic feature of thrombotic microangiopathy (TMA). With this background, the aim of the study was to investigate in a prospective way (1) the relationship among serum Lam-P1, the extent of renal histopathologic lesions, and the biochemical parameters commonly used as markers of TMA activity, and (2) the usefulness of serum Lam-P1 concentrations as a renal outcome prognostic index. To this end, 18 consecutive patients with active biopsy-proven TMA with renal involvement were studied. One hundred and twenty-one healthy control subjects, 20 patients with systemic scleroderma without renal involvement, and 35 patients with systemic lupus erythematosus (20 without nephropathy and 15 with diffuse proliferative type 4 lupus nephritis) were used as control groups. In addition, to analyze the influence of either renal failure or hemodialysis therapy on serum Lam-P1 levels, 91 patients on regular hemodialysis therapy and 81 patients with predialysis chronic renal failure of different etiologies were included in the study. Serum Lam-P1 was determined by RIA at admission, on days 10 and 30 of follow-up in all patients, and after 6 and 12 mo of follow-up in all surviving patients. Serum lactate dehydrogenase, haptoglobin, platelet count, hemoglobin, and serum creatinine were determined as markers of endothelial dysfunction and hemolysis. At admission, serum levels of Lam-P1 were significantly higher in patients with TMA than in healthy control subjects (3.39 +/- 0.56 U/ml versus 1.40 +/- 0.18 U/ml; P < 0.0001). In addition, patients with TMA had significantly higher serum Lam-P1 levels than the other groups included in the study. At the first control, Lam-P1 correlated with lactate dehydrogenase (P = 0.006) and hemoglobin (P = 0.002). During follow-up, platelet count and hemolysis indicators normalized in all patients, while serum Lam-P1 decreased only in patients with renal function recovery. In multivariate analysis, serum creatinine and Lam-P1 at day 10 were the only independent predictors of renal outcome (r2 = 0.94; P < 0.0001) and also correlated with indices of histopathologic damage (P < 0.001). Serum Lam-P1 normalized in all patients with chronic renal failure in the samples obtained at 6 and 12 mo of regular hemodialysis after solving active TMA, thus suggesting that histopathologic lesions, but not renal function itself, would be mainly responsible for the high Lam-P1 serum concentrations detected in TMA. In conclusion, serum Lam-P1 concentrations are increased in patients with active TMA. Furthermore, patients with poor renal outcome show a prolonged increase of serum Lam-P1 that is related to the extent of renal histologic lesions. Unlike the biochemical markers of hemolysis commonly used to assess TMA activity, the sequential determination of serum Lam-P1 provides valuable information about long-term renal prognosis in patients with TMA.